Efficient entrapment of poorly water-soluble pharmaceuticals in hybrid nanoparticles

Tsutomu Ishihara, Maoko Goto, Hideko Kanazawa, Megumu Higaki, Yutaka Mizushima

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Polymeric micelles consisting of amphiphilic block copolymers have emerged as a promising carrier of various drugs, but unfortunately show a limited potential for encapsulating (solubilizing) such drugs. In this study, hybrid nanoparticles consisting of monomethoxypolyethyleneglycol-polylactide block copolymer (PEG-PLA) and oleic acid calcium salt were prepared to enhance the solubilization of poorly watersoluble drugs. Micelles made of a mixture of sodium oleate and PEG-PLA at various ratios were used as the template for preparation of the nanoparticles. These mixed micelles could efficiently solubilize poorly water-soluble drugs in aqueous media, when compared with polymeric micelles made of PEG-PLA alone. Addition of calcium to the mixed micelles induced the formation of oleic acid calcium salt, resulting in hybrid nanoparticles. These hybrid nanoparticles had a high colloidal stability, neutral zeta potential, and high drug entrapment efficiency. Drugs entrapped in nanoparticles made at a high PEG-PLA ratio were protected from enzymatic degradation in serum, while drugs entrapped in the mixed micelles were not, indicating that the hybrid nanoparticles show good drug retention. These results suggested that such hybrid nanoparticles may be used to expand the availability of poorly water-soluble drugs for various therapeutic applications.

Original languageEnglish
Pages (from-to)2357-2363
Number of pages7
JournalJournal of Pharmaceutical Sciences
Volume98
Issue number7
DOIs
Publication statusPublished - 2009 Jul

Fingerprint

Nanoparticles
Micelles
Water
Pharmaceutical Preparations
Oleic Acid
Calcium
Salts
Drug Carriers
monomethoxypolyethyleneglycol-polylactide block copolymer
Serum

Keywords

  • Encapsulation
  • Micelle
  • Nanoparticles
  • Physical stability
  • Poly(lactic/glycolic) acid (PLGA, PLA)
  • Polymeric drug delivery systems

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Efficient entrapment of poorly water-soluble pharmaceuticals in hybrid nanoparticles. / Ishihara, Tsutomu; Goto, Maoko; Kanazawa, Hideko; Higaki, Megumu; Mizushima, Yutaka.

In: Journal of Pharmaceutical Sciences, Vol. 98, No. 7, 07.2009, p. 2357-2363.

Research output: Contribution to journalArticle

Ishihara, Tsutomu ; Goto, Maoko ; Kanazawa, Hideko ; Higaki, Megumu ; Mizushima, Yutaka. / Efficient entrapment of poorly water-soluble pharmaceuticals in hybrid nanoparticles. In: Journal of Pharmaceutical Sciences. 2009 ; Vol. 98, No. 7. pp. 2357-2363.
@article{cfef57ff56fa4afb84511bbc6f14be13,
title = "Efficient entrapment of poorly water-soluble pharmaceuticals in hybrid nanoparticles",
abstract = "Polymeric micelles consisting of amphiphilic block copolymers have emerged as a promising carrier of various drugs, but unfortunately show a limited potential for encapsulating (solubilizing) such drugs. In this study, hybrid nanoparticles consisting of monomethoxypolyethyleneglycol-polylactide block copolymer (PEG-PLA) and oleic acid calcium salt were prepared to enhance the solubilization of poorly watersoluble drugs. Micelles made of a mixture of sodium oleate and PEG-PLA at various ratios were used as the template for preparation of the nanoparticles. These mixed micelles could efficiently solubilize poorly water-soluble drugs in aqueous media, when compared with polymeric micelles made of PEG-PLA alone. Addition of calcium to the mixed micelles induced the formation of oleic acid calcium salt, resulting in hybrid nanoparticles. These hybrid nanoparticles had a high colloidal stability, neutral zeta potential, and high drug entrapment efficiency. Drugs entrapped in nanoparticles made at a high PEG-PLA ratio were protected from enzymatic degradation in serum, while drugs entrapped in the mixed micelles were not, indicating that the hybrid nanoparticles show good drug retention. These results suggested that such hybrid nanoparticles may be used to expand the availability of poorly water-soluble drugs for various therapeutic applications.",
keywords = "Encapsulation, Micelle, Nanoparticles, Physical stability, Poly(lactic/glycolic) acid (PLGA, PLA), Polymeric drug delivery systems",
author = "Tsutomu Ishihara and Maoko Goto and Hideko Kanazawa and Megumu Higaki and Yutaka Mizushima",
year = "2009",
month = "7",
doi = "10.1002/jps.21605",
language = "English",
volume = "98",
pages = "2357--2363",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "John Wiley and Sons Inc.",
number = "7",

}

TY - JOUR

T1 - Efficient entrapment of poorly water-soluble pharmaceuticals in hybrid nanoparticles

AU - Ishihara, Tsutomu

AU - Goto, Maoko

AU - Kanazawa, Hideko

AU - Higaki, Megumu

AU - Mizushima, Yutaka

PY - 2009/7

Y1 - 2009/7

N2 - Polymeric micelles consisting of amphiphilic block copolymers have emerged as a promising carrier of various drugs, but unfortunately show a limited potential for encapsulating (solubilizing) such drugs. In this study, hybrid nanoparticles consisting of monomethoxypolyethyleneglycol-polylactide block copolymer (PEG-PLA) and oleic acid calcium salt were prepared to enhance the solubilization of poorly watersoluble drugs. Micelles made of a mixture of sodium oleate and PEG-PLA at various ratios were used as the template for preparation of the nanoparticles. These mixed micelles could efficiently solubilize poorly water-soluble drugs in aqueous media, when compared with polymeric micelles made of PEG-PLA alone. Addition of calcium to the mixed micelles induced the formation of oleic acid calcium salt, resulting in hybrid nanoparticles. These hybrid nanoparticles had a high colloidal stability, neutral zeta potential, and high drug entrapment efficiency. Drugs entrapped in nanoparticles made at a high PEG-PLA ratio were protected from enzymatic degradation in serum, while drugs entrapped in the mixed micelles were not, indicating that the hybrid nanoparticles show good drug retention. These results suggested that such hybrid nanoparticles may be used to expand the availability of poorly water-soluble drugs for various therapeutic applications.

AB - Polymeric micelles consisting of amphiphilic block copolymers have emerged as a promising carrier of various drugs, but unfortunately show a limited potential for encapsulating (solubilizing) such drugs. In this study, hybrid nanoparticles consisting of monomethoxypolyethyleneglycol-polylactide block copolymer (PEG-PLA) and oleic acid calcium salt were prepared to enhance the solubilization of poorly watersoluble drugs. Micelles made of a mixture of sodium oleate and PEG-PLA at various ratios were used as the template for preparation of the nanoparticles. These mixed micelles could efficiently solubilize poorly water-soluble drugs in aqueous media, when compared with polymeric micelles made of PEG-PLA alone. Addition of calcium to the mixed micelles induced the formation of oleic acid calcium salt, resulting in hybrid nanoparticles. These hybrid nanoparticles had a high colloidal stability, neutral zeta potential, and high drug entrapment efficiency. Drugs entrapped in nanoparticles made at a high PEG-PLA ratio were protected from enzymatic degradation in serum, while drugs entrapped in the mixed micelles were not, indicating that the hybrid nanoparticles show good drug retention. These results suggested that such hybrid nanoparticles may be used to expand the availability of poorly water-soluble drugs for various therapeutic applications.

KW - Encapsulation

KW - Micelle

KW - Nanoparticles

KW - Physical stability

KW - Poly(lactic/glycolic) acid (PLGA, PLA)

KW - Polymeric drug delivery systems

UR - http://www.scopus.com/inward/record.url?scp=67650146638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650146638&partnerID=8YFLogxK

U2 - 10.1002/jps.21605

DO - 10.1002/jps.21605

M3 - Article

C2 - 18979534

AN - SCOPUS:67650146638

VL - 98

SP - 2357

EP - 2363

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 7

ER -